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Study Finds Link Between In-Utero Acetaminophen Use and Child ADHD

A recent study in JAMA Pediatrics caused quite a bit of a stir in finding a possible link between acetaminophen taken during pregnancy and later childhood ADHD. Acetaminophen has been one of the few medications that has been thought to be pretty safe to use during pregnancy and thus has been the “go to” agent for pain, fever, and other indications, especially given the known risks of some of the alternatives such as NSAIDS. Now, however, some people aren’t so sure.

The study used data from the Danish National Birth Cohort and assessed over 64,000 pregnant mothers. The amount of acetaminophen use was measured from computer-assisted telephone interviews. Child behavioral data was collected at age 7 using scores from the Strengths and Difficulties Questionnaire as well as medical records indicating a child took stimulant medications or had an ADHD diagnosis (in this study it was actually ICD hyperkinetic disorder but it is very similar). Hazard ratios, similar to odds ratios, were calculated to compare the risk of ADHD between acetaminophen exposed and non-exposed mothers, controlling for some potential confounding factors such as maternal infections, inflammation, and maternal mental health.

The study found that majority of mothers did use acetaminophen at some time point during pregnancy. Compared to mothers who did not use acetaminophen at all, the risk of ADHD in the offspring of mothers who did was significantly elevated, with hazard ratios ranging between 1.13 and 1.37 depending on how ADHD was measured. As an example, elevated scores related to hyperactivity were found in 5.7% of children whose mothers took any acetaminophen during pregnancy versus 4.3% of children who mothers did not. There was also some evidence that higher overall acetaminophen use and use during later pregnancy was associated with higher ADHD risk.

The authors concluded that in utero acetaminophen exposure was associated with increased rates of ADHD or ADHD-like behaviors and they urged further study to verify the findings. The journal also featured an accompanying editorial which recommended that clinical practice not be fundamentally changed from this single non-controlled study.

The media, for the most part, also seemed to get that message and generally did a decent job of not going overboard with their headlines or text. This was probably good given that everyone seemed to cover the study about a month ago (even I got asked to comment for ABC news). Clearly, the biggest potential concern is the very real possibility that it is the factors that cause a pregnant mother to take acetaminophen, and not the drug itself, that underlies the link with ADHD. While the authors took some steps to account for this possibility, they acknowledged that they could not completely control for it. As there is also some preliminary data linking things like inflammation and infections during pregnancy and child behavioral problems, some restraint prior to changing recommendations seems appropriate. It is one thing to try something that at best is harmless to see if a health benefit can be obtained (even in the absence of great data), but it is quite another scenario when those actions (or lack of action) may make things worse. We will have to see, with the message now perhaps being that no medications, over the counter or not, should be taken casually while pregnant.

What might be the mechanism behind this association? Nobody knows, but the authors did speculate about the possibility that acetaminophen might alter sex or thyroid hormone levels.